Targeting triglycerides to lower residual cardiovascular risk

ABSTRACT

Introduction

Dyslipidemia therapeutics have primarily focused on lowering levels of low-density lipoprotein cholesterol. However, many patients continue to experience cardiovascular events, despite effective lowering of LDL-C. This has prompted efforts to target additional risk factors to achieve more effective prevention of cardiovascular disease. Emerging evidence suggests that triglyceride rich lipoproteins play a causal role in atherosclerosis, highlighting the potential for specific therapeutic lowering.

Areas covered

(1) Evidence to support the causal role of triglyceride rich lipoproteins in atherosclerotic cardiovascular disease. (2) Use of existing lipid modifying therapies to target triglyceride rich lipoproteins. (3) Development of novel therapeutic agents that target triglyceride rich lipoproteins and their potential impact on cardiovascular risk.

Expert Opinion/Commentary

Evidence from preclinical, observational and genetic studies highlight the role of triglyceride rich lipoproteins in the causal pathway of atherosclerotic cardiovascular disease. A number of existing agents have the potential to reduce residual cardiovascular risk associated with hypertriglyceridemia. However, emerging agents have the potential to substantially and preferentially lower triglyceride levels beyond contemporary therapeutics. How they will modulate cardiovascular risk will ultimately be determined by large clinical outcomes trials. They do provide the opportunity to substantially influence the way we target dyslipidemia in the prevention of cardiovascular disease.

KEYWORDS:

• Cardiovascular disease
• lipids
• triglycerides
• risk factors
• atherosclerosis
• clinical trials

Article highlights

• Hypertriglyceridemia associates with residual cardiovascular risk.

• Genetic and preclinical studies directly implicate triglyceride rich lipoproteins in the causality of atherosclerotic disease.

• The presence of hypertriglyceridemia identifies patients who require more intensive lipid lowering.

• Existing agents with the potential to lower cardiovascular risk (fibrates, omega-3 fatty acids) are more likely to be protective in the high triglyceride patient, but not does not associate with triglyceride lowering.

• Novel agents developed to lower triglycerides need further evaluation in clinical trials.

Declaration of Interest

SJ Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Fauna Bio, Resverlogix, New Amsterdam Pharmaceuticals, Novartis, InfraReDx and Sanofi-Regeneron, and is a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, Cardiol Therapeutics, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Nanophagix, New Amsterdam Pharmaceuticals, Takeda, Pfizer, Sanofi-Regeneron and Novo Nordisk. The other authors have potential conflicts to disclose.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript declares that they are a consultant for Amarin Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.